Harnessing stem cells and biomaterials to promote neural repair

Abstract

With the limited capacity for self‐repair in the adult CNS, efforts to stimulate quiescent stem cell populations within discrete brain regions, as well as harness the potential of stem cell transplants, offer significant hope for neural repair. These new cells are capable of providing trophic cues to support residual host populations and/or replace those cells lost to the primary insult. However, issues with low‐level adult neurogenesis, cell survival, directed differentiation and inadequate reinnervation of host tissue have impeded the full potential of these therapeutic approaches and their clinical advancement. Biomaterials offer novel approaches to stimulate endogenous neurogenesis, as well as for the delivery and support of neural progenitor transplants, providing a tissue‐appropriate physical and trophic milieu for the newly integrating cells. In this review, we will discuss the various approaches by which bioengineered scaffolds may improve stem cell‐based therapies for repair of the CNS.

<p>Targetting Exosomes as a New Biomarker and Therapeutic Approach for Alzheimer’s Disease</p>

“…This is because MSCs are involved in multiple biological processes, including neurogenesis, oligodendrogenesis, axonal connectivity, and myelin formation. [73][74][75][76] Around eight years ago, a research study showed that the intravenous delivery of MSCs allowed transport across the blood-brain barrier and subsequent migration to sites of neural injury without inducing tumorigenic or immune responses. 77 MSCs have also been shown to promote cognitive function in various pathological conditions, [78][79][80] including neuro-regeneration, 72 neuroprotection, 79 the reduction of Aβ deposits and tau-related cell death, 80 and the downregulation of pro-inflammatory cytokines, such as TNF-a and IL-1β.…”

Transcription Factor-Based Fate Specification and Forward Programming for Neural Regeneration

“…However, advanced pre-differentiation is typically associated with decreased survival and integration of the grafted cells. Thus, it might be beneficial to implement modalities for continuous delivery of TFs, e.g., by repetitive virus injection or slowrelease depots in form of scaffolds binding or encapsulating fate-specifying proteins such as TFs and/or morphogens (see review by Bruggeman et al, 2019). Prolonged provision of fate-specifying factors beyond the timepoint of transplantation might also enhance the in vivo stability of neuronal subtype identities: Although there are TF-based protocols available to produce quite specific neuronal subtypes in vitro, the results of several studies suggest that TF-mediated acquisition and maintenance of subtype specification might be less efficient in transplanted neurons compared to a pure in vitro scenario (Martinat et al, 2006;Theka et al, 2013;Faedo et al, 2017;Yuan et al, 2018).…”

Neuronal Replacement as a Tool for Basal Ganglia Circuitry Repair: 40 Years in Perspective

“…Also, there is an increasing interest in the role and potential of extracellular matrix proteins, such as laminin and fibronectin, due to their ability to promote the survival, proliferation, and differentiation of fetal and hPSC-derived neural progenitors (Kirkeby et al, 2017b;Somaa et al, 2017;Zhang et al, 2017). For a comprehensive overview of these promising developments, the reader is referred to the recent reviews by Bruggeman et al (2019) and Moriarty et al (2019b).…”